PAPER 551 Iodobenzene Dichloride as a Stoichiometric Oxidant for the Conversion of Alcohols into Carbonyl Compounds; Two Facile Methods for Its Preparation SynthesisXue-Fei and Use of Iodobenzene Dichloride Zhao, Chi Zhang* The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. of China Fax +86(22)23499247; E-mail: [email protected] Received 15 September 2006; revised 8 November 2006 ported that iodobenzene dichloride oxidized secondary al- Abstract: A highly efficient and mild procedure is described for the cohols to the corresponding ketones in moderate yields in oxidation of different types of alcohols using 2,2,6,6-tetramethylpi- 11 peridin-1-yloxy (TEMPO) as the catalyst, iodobenzene dichloride the presence of pyridine. The main drawback to this sim- (PhICl2) as a stoichiometric oxidant, and pyridine as the base. This ple system was its inability to oxidize primary alcohols to procedure also smoothly oxidizes 1,2-diols to a-hydroxy ketones or the corresponding aldehydes. Herein, we report the use of a-diketones depending upon the amount of iodobenzene dichloride a 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO) cata- used. A competitive study shows that using the 2,2,6,6-tetrameth- lyzed oxidation system with iodobenzene dichloride as ylpiperidin-1-yloxy/iodobenzene dichloride/pyridine system ali- the stoichiometric oxidant and pyridine as the base for the phatic secondary alcohols are preferentially oxidized over aliphatic primary alcohols. In addition, two very convenient and high yield- oxidization of primary and secondary alcohols to the cor- ing procedures for the preparation of iodoarene dichlorides from io- responding aldehydes and ketones in excellent yields. We doarenes have been developed. One employs solid sodium chlorite also report two efficient, easily handled, and environmen- as a chlorinating agent in dilute hydrochloric acid solution; the other tally benign procedures for the preparation of iodoarene uses sodium hypochlorite as a chlorinating agent still in hydrochlo- dichlorides from iodoarenes. ric acid solution, which is more robust than the sodium chlorite sys- tem. Typically, the preparation of iodobenzene dichloride from In the course of investigating the oxidative properties of iodobenzene was performed in five minutes using the sodium hy- iodobenzene dichloride, we found that decan-1-ol was ox- pochlorite/hydrochloric acid system. idized to decanal in quantitative yield with TEMPO (8 Key words: iodobenzene dichloride, alcohols, catalysis, TEMPO, mol%), iodobenzene dichloride (1.5 equiv), and pyridine oxidation (3 equiv) in chloroform (10 mL) at 50 °C (oil bath) for six hours. Reducing the loading of catalyst TEMPO from 8 mol% to 5 mol% resulted in a decreased yield of decanal Iodobenzene dichloride, the first reported hypervalent io- (82%). When the reaction was carried out at room temper- dine reagent, was synthesized by C. Willgerodt in 1886.1 ature, the yield of decanal was 80% even after 18 hours. Historically, it has been principally used as a chlorinating The concentration effect was apparent in this reaction reagent in organic synthesis replacing gaseous chlorine.2 since the reaction time was shortened from six to three Typically, Garvey, Halley, and Allen first observed that hours when the volume of chloroform was reduced from the reaction of iodobenzene dichloride with unsaturated 10 mL to 5 mL. In addition, in the absence of pyridine, the hydrocarbons in refluxing 1,2-dichloroethane gave the conversion of decan-1-ol was only 54% and decanal was same products as when chlorine gas was used.3 Breslow et obtained in 48% yield after 18 hours. The solvent effect al. have shown a number of beautiful examples of tem- on the oxidation of decan-1-ol was also examined, the re- plate-directed chlorination of the C–H bond in steroids us- sults are summarized in Table 1. ing iodobenzene dichloride as the chlorinating agent.4 As shown in Table 1, chloroform appears to be the best Moreover, numerous applications of iodobenzene dichlo- solvent among those tested, affording decanal in 94% ride for the introduction of element chlorine into various metal complexes have also been described.5 Another im- Table 1 Screened Solvents for the Oxidation of Decan-1-ola pressive use of iodobenzene dichloride is its combination with lead(II) thiocyanate to effect the thiocyanation of Entry Solvent Time (h) Yield (%) 6 various organic substrates including silyl enol ethers, b- 1CHCl3 394 dicarbonyl compounds,6 alkynes,7 phenols and naph- thols.8 However, it appeared that the synthetic utility of 2CH2Cl2 350 iodobenzene dichloride as an oxidizing agent was fairly 3THF369 limited; the oxidation of aldoximes to nitrile oxides9 and oxidative deoximation of ketoximes to the corresponding 4 PhMe 3 62 10 ketones are two examples. In addition, Wicha et al. re- 5EtOAc356 6MeCN357 SYNTHESIS 2007, No. 4, pp 0551–0557 xx .xx .2 0 07 a Reactions were performed with decan-1-ol (1 mmol), TEMPO (8 Advanced online publication: 12.01.2007 mol%), PhICl (1.5 equiv), pyridine (3 equiv), solvent (5 mL), 50 °C. DOI: 10.1055/s-2007-965889; Art ID: F15306SS 2 © Georg Thieme Verlag Stuttgart · New York 552 X.-F. Zhao, C. Zhang PAPER TEMPO (8 mol%) CH -(CH ) -CH OH + PhICl (1.5 equiv) CH -(CH ) -CHO 3 2 8 2 2 3 2 8 pyridine (3 equiv) 94% (5 mL), 50 °C, 3 h CHCl 3 Scheme 1 Optimal reaction conditions for the oxidation of decan-1-ol yield (Table 1, entry 1). The yield of decanal was only It was observed that longer reaction times were required 50% when reaction was performed in dichloromethane; a for the oxidation of primary aliphatic alcohols compared major factor in this case was the poor solubility of iodo- with that for a secondary alcohol (Table 2, entries 1, 2, benzene dichloride in dichloromethane (Table 1, entry 2). and 3 vs entry 4). A competitive study was conducted in Consequently, the optimal reaction parameters were fixed which a mixture of decan-1-ol (1 mmol) and octan-2-ol (1 and are given in Scheme 1. mmol) was oxidized using 1.05 mmol of iodobenzene A variety of alcohols, such as aliphatic primary and sec- dichloride and decanal and octan-2-one were obtained in ondary alcohols, benzylic and allylic alcohols, were oxi- a 1:4.4 ratio. This finding confirmed that the TEMPO/ dized to the corresponding carbonyl compounds in good iodobenzene dichloride/pyridine oxidation system prefer- to excellent yields. Like decan-1-ol, two other aliphatic entially oxidizes secondary alcohols over primary alco- primary alcohols with shorter or longer carbon chains, oc- hols (Scheme 2). It should be noted that iodobenzene diacetate/TEMPO preferentially oxidizes primary alco- tan-1-ol and hexadecan-1-ol were smoothly oxidized to 12 their corresponding aldehydes in excellent yields hols over secondary alcohols. (Table 2, entries 2 and 3). As for secondary alcohols, oc- The mechanism of this alcohol oxidation reaction is worth tan-2-ol and menthol were oxidized to the corresponding discussing. Firstly, the fact that the efficiency of this reac- ketones in 98% and 93% yields, respectively (Table 2, en- tion decreased dramatically in the absence of pyridine tries 4 and 5). 1-Phenylethanol and benzyl alcohol were suggested that this reaction is not an acid-catalyzed excellent substrates under the standard oxidation condi- TEMPO dismutation process to give an oxoammonium tions since their corresponding products were obtained in salt, which operated in a fairly similar oxidation system, 94% and quantitative yield, respectively (Table 2, entries iodobenzene diacetate/TEMPO.12 Accordingly, it is pro- 6 and 7). Notably, (2Z)-4-(tetrahydropyran-2-yloxy)but- posed that TEMPO is oxidized to its oxoammonium salt, 2-en-1-ol was oxidized to the corresponding aldehyde in which, as previously reported, is capable of oxidizing al- 77% yield without isomerization of the double bond (Table 2, entry 8). Table 2 Oxidation of Various Alcohols with Iodobenzene Dichlo- a The iodobenzene diacetate/TEMPO system developed by ride Piancatelli et al. performs very well for the oxidization of Entry Alcohol Time Product Yieldb various primary and secondary alcohols and 1,3-diols to (%) their corresponding carbonyl compounds; 1,2-diols are, however, cleaved to give the corresponding aldehydes.12 1 decan-1-ol 3 h decanal 94 In our system, 1,2-diols could be successfully oxidized to 2 octan-1-ol 3 h octanal 89 their corresponding a-hydroxy ketones or a-diketones de- pending upon the number of equivalents of iodobenzene 3 hexadecan-1-ol 4.5 h hexadecanal 92 dichloride used. For example, cyclooctane-1,2-diol was 4 octan-2-ol 1 h octan-2-one 98 oxidized using 1.1 equivalents of iodobenzene dichloride to give 2-hydroxycyclooctan-1-one in 85% yield together 5 menthol 45 min menthone 93 with cyclooctane-1,2-dione in 10% yield (Table 3, entry 6 1-phenylethanol 40 min acetophenone 94 1). Increasing the amount of iodobenzene dichloride to three equivalents gave cyclooctane-1,2-dione in quantita- 7 benzyl alcohol 40 min benzaldehyde >99c tively yield as the sole product (Table 3, entry 2). In the 8 1.5 h 77 THPO CH OH THPO case of 1,2-diphenylethane-1,2-diol, as benzil is more sta- CHO ble than benzoin due to the conjugate effect, the ratio of a- 2 a hydroxy ketone (benzoin) to a-diketone (benzil) is only Reaction conditions: alcohol (1 mmol), TEMPO (8 mol%), PhICl2 1.9:1 with 1.1 equivalents of iodobenzene dichloride, (1.5 equiv), pyridine (3 equiv), CHCl3 (5 mL), 50 °C b Isolated yield. which is much lower than in the case of cyclooctane-1,2- c GC yield. diol (1.9:1 vs 8.5:1; Table 3, entry 3 vs entry 1).